Sterilization with a germicidal agent, such as ethylene oxide gas or ethylene oxide containing gas mixtures, has played an increasingly important role in sterilizing heat or moisture sensitive materials. Rapid growth in the use of sterile, disposable medical devices is just one consequence of gaseous sterilization with agents such as ethylene oxide. Gaseous sterilization of re-useable medical and surgical equipment using a nonflammable mixture of ethylene oxide and a carrier gas has also proven to be reliable, cost effective technology for many hospitals.
The basic gaseous sterilization process consists of evacuating the sterilization chamber containing articles to be sterilized, preconditioning the articles at an optimal relative humidity, generally between 20-70%, admitting the sterilizing gas at an appropriate pressure and temperature, maintaining contact between the sterilizing atmosphere and the articles to be sterilized for an appropriate time, and finally discharging and evacuating the chamber to remove the sterilant gas.
Although there are many variations on the basic process, the major factors which have to be controlled in order to effect the sterilization are exposure time, temperature, ethylene oxide pressure or partial pressure, and relative humidity. The following prior art references provide a good description of the standard sterilization processes and apparatus with which the gaseous sterilizing agents of the invention are useful: J. J. Perkins, Principles and Methods of Sterilization, at 501-530 (2d ed. 1969); and Ethylene Oxide Gaseous Sterilization For Industrial Applications, Industrial Sterilization International Symposium, 181-208 (1972), U.S. Pat. No. 3,068,064 and U.S. Pat. No. 3,589,861.
By itself, ethylene oxide is an extremely flammable gas. Its flammability range extends from about 3.0% by volume to 100% by volume in air. Thus, when ethylene oxide is used alone as a sterilizing gas, precautions such as explosion proof equipment are mandatory.
A preferable practice is to blend the ethylene oxide with another fluid which serves to dilute the ethylene oxide and render the mixture as a whole, nonflammable. Two such blends which have been used as sterilizing gases are dichlorodifluoromethane (CFC-12)/ethylene oxide and carbon dioxide/ethylene oxide. Inert carrier gases like CFC-12 and carbon dioxide inhibit the flammability of ethylene oxide and provide sufficient autogeneous vapor pressure to deliver the liquid mixture from the source cylinder to the heat exchanger of the sterilizer vessel where the liquid mixture is vaporized.
The CFC-12/ethylene oxide blend is generally supplied as a liquid mixture consisting of 88% by weight CFC-12 and 12% by weight ethylene oxide. This composition is below the critical flammability composition of about 14-15% by weight ethylene oxide in CFC-12, and is therefore nonflammable. A typical hospital sterilization process which utilizes the CFC-12/ethylene oxide blend is performed by evacuating the chamber containing the articles to about 20-24 inches of mercury vacuum, preconditioning the articles at an optimal relative humidity, and filling the chamber to about 10 psig pressure with the gas mixture. Sterilization is generally performed around 130.degree. F. The 88/12 by weight CFC-12/ethylene oxide mixture produces a gas mixture containing 72.8 volume or mole percent CFC-12 and 27.2 volume or mole percent ethylene oxide. This composition provides about 630 milligrams of ethylene oxide per liter at the stated typical operating condition. The concentration (mg/liter) of ethylene oxide present in the sterilization chamber is critical in determining the required exposure time and ultimate sterilization efficiency. The Association for the Advancement of Medical Instrumentation (AAMI) recommends an absolute minimum ethylene oxide concentration of 450 mg/liter.
The nonflammable carbon dioxide/ethylene oxide blend is also supplied as a liquid mixture consisting of about 90% by weight carbon dioxide and about 10% by weight ethylene oxide. This blend produces a gas mixture containing 90% by volume or mole carbon dioxide and 10% by volume or mole ethylene oxide. The available ethylene oxide concentration (mole percent) is significantly less than that obtained from the 88/12 by weight CFC-12/ethylene oxide blend. Sterilization using carbon dioxide/ethylene oxide is generally performed at a greater pressure then that used with CFC-12/ethylene oxide to increase the concentration of ethylene oxide, or is performed for greater exposure time which decreases productivity.
A disadvantage of using CFC-12 in sterilant gas mixtures is that fully halogenated chlorofluorocarbons such as CFC-12 have been implicated in causing environmental problems. Specifically, CFC-12 has substantial potential for stratospheric ozone depletion and global warming.
Although the major purpose of the inert carrier gas component in these sterilizing gas mixtures is to mask the flammability characteristics of ethylene oxide, simple substitution of an arbitrary nonflammable gas does not necessarily ensure a useful sterilizing gas mixture. First, the flammability properties of the blend must be such that a sufficient amount of ethylene oxide (mg/liter at a typical pressure and temperature) is delivered by the blend to effect the sterilization in an appropriate time. If the carrier gas does not mask the flammability to a sufficient extent, a lower concentration of ethylene oxide must be used to ensure nonflammability. In such a case either a longer exposure time is required to perform the sterilization, which affects productivity, or greater operating pressures are required to increase the effective ethylene oxide density in the sterilization chamber. Increasing the operating pressure is generally not a viable alternative because existing sterilization chambers may not be rated for the increased pressure, and as pointed out by Gunther in U.S. Pat. No. 3,589,861, increased pressure can lead to swelling and rupture of the sealed plastic bags commonly used to package disposable medical devices. Indeed, lower operating pressures are advantageous in this respect. The need for a greater operating pressure or increased exposure time has limited the acceptance of the 90/10 carbon dioxide/ethylene oxide mixture in comparison to the 88/12 CFC-12/ethylene oxide mixture.
A candidate inert diluent or carrier gas must also be miscible with ethylene oxide in the liquid phase and must not segregate from the ethylene oxide to any great extent during vaporization. Segregation or fractionation can lead to potentially flammable or explosive situations. The degree of segregation that may occur during evaporation is related to the relative volatility of the components of the mixture. The vapor pressure of ethylene oxide at 70.degree. F. is 22 psia while the vapor pressures of CFC-12 and carbon dioxide at 70.degree. F. are 85 and 850 psia, respectively. The vapor pressure data indicate a very large difference in volatility between carbon dioxide and ethylene oxide, and hence a susceptibility for carbon dioxide/ethylene oxide blends to fractionate.
Kaye, in U.S. Pat. No. 2,891,838 discloses sterilizing compositions comprising ethylene oxide, CFC-12, and CFC-11 (trichlorofluoromethane). In this instance the ethylene oxide is blended with two other components, one which is more volatile (CFC-12) than ethylene oxide and the other which is less volatile (CFC-11) than ethylene oxide, reducing the potential for fractionation into the flammable region. This particular 3-component blend has not been widely accepted because of material compatibility problems, i.e., CFC-11 is incompatible with some plastic or polymeric materials.
Thus, the need exists for a carrier gas which is compatible with the objects being sterilized; chemically stable; environmentally acceptable; minimally segregating; contains at least 27 mole percent ethylene oxide; and provides sufficient vapor pressure to deliver the liquid mixture to the sterilization chamber.
Accordingly, it is an object of the invention to provide a novel sterilizing gas mixture containing ethylene oxide.
It is an object of the invention to provide such a sterilizing gas mixture which contains an inert fluorocarbon diluent, or diluents, which are considered to be environmentally acceptable.
Another object of the invention is to provide a nonflammable gas mixture which is capable of providing a gas phase concentration (mole percent or mg/liter) of ethylene oxide equivalent to or in excess of that concentration provided by 88/12 CFC-12/ethylene oxide.
It is another object of the invention to provide a sterilizing gas mixture which is miscible and minimally segregating.
Another object of the invention is to provide a sterilizing gas mixture with sufficient vapor pressure to deliver the liquid mixture to the sterilization chamber.
Still another object of this invention is to provide a sterilizing gas mixture which is compatible with plastic and polymers used in the construction of medical devices.
Other objects and advantages of the invention will become apparent from the following description of the invention.
SUMMARY OF THE INVENTION
The invention relates to compositions which are useful in gas sterilization processes. Specifically, the invention relates to novel sterilant gas compositions comprising effective amounts of monochlorotetrafluoroethane and ethylene oxide which are environmentally acceptable, possess improved flammability suppressant characteristics, and are capable of maintaining a greater ethylene oxide concentration than traditional sterilizing gas compositions.